PROJECT SUMMARY This proposal describes a five-year career development and training plan for Dr. Umesh Sharma under the mentorship of Professor John M. Canty, Jr. Dr. Sharma is currently an Assistant Professor of Medicine at University at Buffalo. His career development plan, that leverages the extensive resources offered by the University and Clinical and Translational Research Center at Buffalo, brings together a strong team of investigators with expertise in small animal physiology, myocardial remodeling, therapeutics and dynamic magnetic resonance imaging. During the period of funding, Dr. Sharma will have a faculty position in the Division of Cardiovascular Medicine at University at Buffalo. His goal is to become a successful and independent investigator studying mechanisms of ischemia-induced myocardial injury and dysfunction, and identify novel therapeutic targets. Receipt of this award will allow Dr. Sharma obtain additional training in small-animal research, comprehensive cardiac tissue and molecular imaging, biostatistics, research design and ethics, and will facilitate his transition to research independence. Dr. Sharma hypothesizes that in presence of ischemic myocardial injury, excess galectin-3 promotes myocardial inflammation and fibrosis. Blocking galectin-3 activity via genetic mutation or therapeutic antagonism inhibits inflammation, reduces fibrosis and preserves cardiac function. Dr. Sharma has a strong research track-record and has obtained excellent preliminary results that show the feasibility of this approach in a murine model of myocardial ischemia. In summary, by bringing together cutting edge technology and a well-rounded team of experts in the setting of excellent research plan and mentorship structure, Dr. Sharma will be able to synergistically merge the fields of advanced imaging, myocardial remodeling and therapeutic targeting using novel liposome-based peptide delivery system. Through this mechanism, Dr. Sharma will obtain support and training to elaborate the skills essential for him to become an independent investigator.